| Autor: |
Cousins, Katheryn A Q, Irwin, David J., Chen‐Plotkin, Alice, Shaw, Leslie M., Arezoumandan, Sanaz, Lee, Eddie B, Wolk, David A., Weintraub, Daniel, Spindler, Meredith, Deik, Andres, Grossman, Murray, Tropea, Thomas F. |
| Zdroj: |
Alzheimer's & Dementia: The Journal of the Alzheimer's Association; Dec2023 Supplement 15, Vol. 19, p1-4, 4p |
| Abstrakt: |
Background: While α‐synuclein (αSyn) is the primary pathology associated with Lewy body spectrum disorders (LBSD), concomitant Alzheimer's disease (AD) pathology is common and is predictive of clinical outcomes, including worse cognitive impairment and shorter survival. Thus, AD plasma biomarkers may help identify clinically relevant co‐pathology in LBSD to improve prognosis and clinical management. Plasma phosphorylated tau 181 (p‐tau181) and glial fibrillary acidic protein (GFAP) are two biomarkers that have been well‐studied in canonical AD, showing reliable increases with AD neuropathological change (ADNC). However, their utility in autopsy‐confirmed LBSD is relatively untested. Method: In autopsy‐confirmed LBSD with a neuropathological diagnosis of αSyn, we tested how plasma p‐tau181 and GFAP differed across αSyn with concomitant ADNC (αSyn+AD; n = 19) and αSyn without AD (αSyn; n = 30). αSyn+AD was defined by intermediate/high ADNC and αSyn had no/low ADNC; cognitively normal controls and AD without αSyn were included as reference groups (Table 1). Severity of burden was scored on a semi‐quantitative scale for β‐amyloid and tau, and scores were averaged across sampled brainstem, limbic, and neocortical regions. Plasma analytes were log‐transformed in linear models, and models covaried for plasma‐to‐death, age at plasma, and sex. Receiver operating characteristic (ROC) analyses and area under the curve (AUC) tested diagnostic utility of plasma analytes. Result: Plasma GFAP was significantly higher in αSyn+AD compared to αSyn (Figure 1), confirmed by linear models (β = 0.31, 95%CI = 0.065 – 0.56, p = 0.015); plasma p‐tau181 was not (p = 0.37). Next, linear models tested associations of AD pathological hallmarks with both plasma analytes. GFAP was significantly associated with brain β‐amyloid (β = 15, 95%CI = 6.1 – 25, p = 0.0018) and tau burden (β = 12, 95%CI = 2.5 – 22, p = 0.015); in the same model plasma p‐tau181 was not associated with either (both p>0.34). ROC analyses showed that neither analyte had an AUC>0.80 (Figure 2); GFAP had somewhat higher AUC of ADNC in LBSD (0.71; 90%CI = 0.58 – 0.83) than plasma p‐tau181 (AUC = 0.64; 90%CI = 0.50 – 0.77). Conclusion: Results demonstrate elevated plasma GFAP in LBSD with concomitant AD pathology, in association with accumulation of β‐amyloid plaques. Findings highlight the importance of validating utility of AD biomarkers in LBSD, and the need for plasma biomarker strategies to detect concomitant AD in LBSD. [ABSTRACT FROM AUTHOR] |
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